Length functions on currents and applications to dynamics and counting

The aim of this (mostly expository) article is twofold. We first explore a variety of length functions on the space of currents, and we survey recent work regarding applications of length functions to counting problems. Secondly, we use length functions to provide a proof of a folklore theorem which states that pseudo-Anosov homeomorphisms of closed hyperbolic surfaces act on the space of projective geodesic currents with uniform north-south dynamics.Comment: 35pp, 2 figures, comments welcome! Second version: minor corrections. To appear as a chapter in the forthcoming book "In the tradition of Thurston" edited by V. Alberge, K. Ohshika and A. Papadopoulo

Fluorescence Photooxidation with Eosin - a Method for High-Resolution Immunolocalization and in-Situ Hybridization Detection for Light and Electron-Microscopy

A simple method is described for high-resolution light and electron microscopic immunolocalization of proteins in cells and tissues by immunofluorescence and subsequent photooxidation of diaminobenzidine tetrahydrochloride into an insoluble osmiophilic polymer. By using eosin as the fluorescent marker, a substantial improvement in sensitivity is achieved in the photooxidation process over other conventional fluorescent compounds. The technique allows for precise correlative immunolocalization studies on the same sample using fluorescence, transmitted light and electron microscopy. Furthermore, because eosin is smaller in size than other conventional markers, this method results in improved penetration of labeling reagents compared to gold or enzyme based procedures. The improved penetration allows for three-dimensional immunolocalization using high voltage electron microscopy. Fluorescence photooxidation can also be used for high resolution light and electron microscopic localization of specific nucleic acid sequences by in situ hybridization utilizing biotinylated probes followed by an eosin-streptavidin conjugate

Trans-generational epigenetic regulation associated with the amelioration of Duchenne Muscular Dystrophy

Exon skipping is an effective strategy for the treatment of many Duchenne Muscular Dystrophy (DMD) mutations. Natural exon skipping observed in several DMD cases can help in identifying novel therapeutic tools. Here, we show a DMD study case where the lack of a splicing factor (Celf2a), which results in exon skipping and dystrophin rescue, is due to a maternally inherited trans-generational epigenetic silencing. We found that the study case and his mother express a repressive long non-coding RNA, DUXAP8, whose presence correlates with silencing of the Celf2a coding region. We also demonstrate that DUXAP8 expression is lost upon cell reprogramming and that, upon induction of iPSCs into myoblasts, Celf2a expression is recovered leading to the loss of exon skipping and loss of dystrophin synthesis. Finally, CRISPR/Cas9 inactivation of the splicing factor Celf2a was proven to ameliorate the pathological state in other DMD backgrounds establishing Celf2a ablation or inactivation as a novel therapeutic approach for the treatment of Duchenne Muscular Dystrophy

A simple echocardiographic score to rule out cardiac amyloidosis

BACKGROUND: Early diagnosis of cardiac amyloidosis (CA) is warranted to initiate specific treatment and improve outcome. The amyloid light chain (AL) and inferior wall thickness (IWT) scores have been proposed to assess patients referred by hematologists or with unexplained left ventricular (LV) hypertrophy, respectively. These scores are composed of 4 or 5 variables, respectively, including strain data. METHODS: Based on 2 variables common to the AL and IWT scores, we defined a simple score named AMYLoidosis Index (AMYLI) as the product of relative wall thickness (RWT) and E/e' ratio, and assessed its diagnostic performance. RESULTS: In the original cohort (n=251), CA was ultimately diagnosed in 111 patients (44%). The 2.22 value was selected as rule-out cut-off (negative likelihood ratio [LR-] 0.0). In the hematology subset, AL CA was diagnosed in 32 patients (48%), with 2.36 as rule-out cut-off (LR- 0.0). In the hypertrophy subset, ATTR CA was diagnosed in 79 patients (43%), with 2.22 as the best rule-out cut-off (LR- 0.0). In the validation cohort (n=691), the same cut-offs proved effective: indeed, there were no patients with CA in the whole population or in the hematology or hypertrophy subsets scoring <2.22, <2.36 or <2.22, respectively. CONCLUSIONS: The AMYLI score (RWT* E/e') may have a role as an initial screening tool for CA. A <2.22 value excludes the diagnosis in patients undergoing a diagnostic screening for CA, while a <2.36 and a <2.22 value may be better considered in the subsets with suspected cardiac AL amyloidosis or unexplained hypertrophy, respectively

Method: automatic segmentation of mitochondria utilizing patch classification, contour pair classification, and automatically seeded level sets

<p>Abstract</p> <p>Background</p> <p>While progress has been made to develop automatic segmentation techniques for mitochondria, there remains a need for more accurate and robust techniques to delineate mitochondria in serial blockface scanning electron microscopic data. Previously developed texture based methods are limited for solving this problem because texture alone is often not sufficient to identify mitochondria. This paper presents a new three-step method, the Cytoseg process, for automated segmentation of mitochondria contained in 3D electron microscopic volumes generated through serial block face scanning electron microscopic imaging. The method consists of three steps. The first is a random forest patch classification step operating directly on 2D image patches. The second step consists of contour-pair classification. At the final step, we introduce a method to automatically seed a level set operation with output from previous steps.</p> <p>Results</p> <p>We report accuracy of the Cytoseg process on three types of tissue and compare it to a previous method based on Radon-Like Features. At step 1, we show that the patch classifier identifies mitochondria texture but creates many false positive pixels. At step 2, our contour processing step produces contours and then filters them with a second classification step, helping to improve overall accuracy. We show that our final level set operation, which is automatically seeded with output from previous steps, helps to smooth the results. Overall, our results show that use of contour pair classification and level set operations improve segmentation accuracy beyond patch classification alone. We show that the Cytoseg process performs well compared to another modern technique based on Radon-Like Features.</p> <p>Conclusions</p> <p>We demonstrated that texture based methods for mitochondria segmentation can be enhanced with multiple steps that form an image processing pipeline. While we used a random-forest based patch classifier to recognize texture, it would be possible to replace this with other texture identifiers, and we plan to explore this in future work.</p

Heterotopic gastrointestinal cyst mimicking chronic cholecystitis: a case report

<p>Abstract</p> <p>Introduction</p> <p>Heterotopic gastric mucosa is described almost everywhere in the gastrointestinal tract, from the oral cavity to the rectum. The occurrence of heterotopic gastric tissue in the gallbladder is rare. A choristoma can be defined as a new growth developing from a displaced anlage not normally present in the anatomical site where it developed. We present an extremely uncommon case of a cyst (choristoma) attached to the gallbladder, which contained gastric and intestinal mucosa.</p> <p>Case presentation</p> <p>A 33-year-old woman was hospitalized with clinical symptoms of chronic cholecystitis. The laboratory findings were within the normal range. Abdominal ultrasonography revealed a thickened gallbladder wall and a stone in the cystic duct was suspected. In the course of laparoscopic cholecystectomy, a cyst was visualized in the vicinity of the duct and the gallbladder neck. Microscopic examination of the removed cyst revealed evidence of gastric, duodenal and small-intestinal mucosa. The immunohistochemical study revealed many endocrine cells, which were positive for several endocrine cell markers such as chromogranin, serotonin, gastrin and so on. It can be inferred that the observed cyst had arisen from the foregut early in the development of the gastrointestinal tract.</p> <p>Conclusion</p> <p>The presence of endocrine cells together with epithelial cells supports the hypothesis that these had developed simultaneously, and that the endocrine cells had probably supported the development of the epithelial cells by the release of hormones and growth factors. To the best of the authors' knowledge, this report is the first to report a gastrointestinal cyst choristoma with endocrine cells in the region of the cystic duct and gallbladder.</p

Test, Reliability and Functional Safety Trends for Automotive System-on-Chip

This paper encompasses three contributions by industry professionals and university researchers. The contributions describe different trends in automotive products, including both manufacturing test and run-time reliability strategies. The subjects considered in this session deal with critical factors, from optimizing the final test before shipment to market to in-field reliability during operative life

Recent EUROfusion Achievements in Support of Computationally Demanding Multiscale Fusion Physics Simulations and Integrated Modeling

Integrated modeling (IM) of present experiments and future tokamak reactors requires the provision of computational resources and numerical tools capable of simulating multiscale spatial phenomena as well as fast transient events and relatively slow plasma evolution within a reasonably short computational time. Recent progress in the implementation of the new computational resources for fusion applications in Europe based on modern supercomputer technologies (supercomputer MARCONI-FUSION), in the optimization and speedup of the EU fusion-related first-principle codes, and in the development of a basis for physics codes/modules integration into a centrally maintained suite of IM tools achieved within the EUROfusion Consortium is presented. Physics phenomena that can now be reasonably modelled in various areas (core turbulence and magnetic reconnection, edge and scrape-off layer physics, radio-frequency heating and current drive, magnetohydrodynamic model, reflectometry simulations) following successful code optimizations and parallelization are briefly described. Development activities in support to IM are summarized. They include support to (1) the local deployment of the IM infrastructure and access to experimental data at various host sites, (2) the management of releases for sophisticated IM workflows involving a large number of components, and (3) the performance optimization of complex IM workflows.This work has been carried out within the framework of the EUROfusion Consortium and has received funding from the Euratom research and training programme 2014 to 2018 under grant agreement 633053. The views and opinions expressed herein do not necessarily reflect those of the European Commission or ITER.Peer ReviewedPostprint (published version